Description: The long term objectives of this proposal are to understand the cellular and molecular mechanisms that underlie the capacity of the cerebral cortex to adapt to changes in patterns of input from the peripheral sense organs in adults. These mechanisms probably not only play a role in the fundamental processes involved in the learning of skills and the capacity to make perceptive judgements about the external world but also appear to be involved in the aberrant perceptions that accompany perturbed peripheral sensory input, for example in the case of pain of central nervous origin. The proposed studies, to be carried out in macaque monkeys, involve deprivation of sensory input from the hand and arm by peripheral nerve section or reversible conduction block, and enhanced input by electrical stimulation, the induction of acute arthritis or innocuous tactile, self-stimulation. The hand representation of the first somatosensory area of the cerebral cortex (SI) will be examined by immunocytochemical, receptor binding and in situ hybridization histochemistry to detect changes in gene expression for molecules that form the components of the gamma aminobutyric acid (GABA) and glutamate containing neuronal systems of the cortex. Changes in the representation pattern in Sl that accompany these will be mapped by multiunit recording. The effects of activity-dependent, up-or down-regulation of transmitter related molecules will be assayed by single unit/iontophoretic studies GABA and glutamate agonists and antagonists. A potential underlying basis of activity dependent plasticity, in widespread intracortical terminations of single thalamocortical axons, will be examined in correlative neuroanatomical tracing studies.